Method for detecting fluid in cranium via time varying magnetic field phase shifts

ABSTRACT

A diagnostic method for monitoring changes in a fluid medium in a patient&#39;s head. The method includes positioning a transmitter at a first location on or near the patient&#39;s head, the transmitter generates and transmits a time-varying magnetic field into a fluid medium in the patient&#39;s head responsive to a first signal; positioning a receiver at a second location on or near the patient&#39;s head offset from the transmitter, the receiver generates a second signal responsive to a received magnetic field at the receiver; transmitting a time-varying magnetic field into the fluid medium in the patient&#39;s head in response to the first signal; receiving the transmitted magnetic field; generating the second signal responsive to the received magnetic field; and determining, a phase shift between the transmitted magnetic field and the received magnetic field for a plurality of frequencies of the transmitted time-varying magnetic field.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of Ser. No. 14/690,985,entitled “Method for Detecting Fluid in Cranium Via Time VaryingMagnetic Field Phase Shifts,” filed Apr. 20, 2015, which is acontinuation application of Ser. No. 14/275,549, entitled “Method forDetecting and Treating Variations in Fluid” filed May 12, 2014, nowabandoned, which is a continuation of U.S. patent application Ser. No.13/745,710, entitled “Diagnostic Method for Detection of Fluid ChangesUsing Shielded Transmission Lines as Transmitters or Receivers,” filedJan. 18, 2013, now U.S. Pat. No. 8,731,636. which claims priority toU.S. provisional patent application No. 61/588,516, filed on Jan. 19,2012, entitled “Diagnostic Device for Detection of Fluid Changes in theBrain and Other Areas of the Body,” all of which are hereby incorporatedby reference in their entireties.

TECHNICAL FIELD

This application is related to noninvasive, diagnostic, medical devices,systems and methods. More specifically, some embodiments of thisdisclosure relate to devices, systems and methods that use magneticinduction phase-shift spectroscopy (“MIPS”) to monitor changes in fluidsin the brain or other parts of the body.

BACKGROUND

In many different medical settings, it would be advantageous to be ableto detect changes in bodily fluids as they occurred in a noninvasivemanner. For example, it is often critical to monitor intracranialchanges in fluid in an intensive care unit patient. Standard of care forthese patients includes invasive monitors that require drilling a holein the cranium and inserting a probe such as an intracranial pressure(ICP) monitor, or microdialysis or “licox” probes for measuring chemicalchanges to the fluids in the brain. No noninvasive measurementtechniques are currently commercially available for detecting cerebralfluid changes such as would occur with bleeding or edema, and many braininjuries are not severe enough to warrant drilling a hole in the craniumfor invasive monitoring. Thus, for many patients with brain injury,there is no continuous monitoring technology available to alert clinicalstaff when there is a potentially harmful increase in edema or bleeding.Instead, these patients are typically observed by nursing staff,employing a clinical neurological examination, and it is not untilincreased fluid in the brain causes observable brain function impairmentthat the physicians or nurses can react. In other words, there is no waycurrently available for monitoring intracranial fluid changesthemselves, and thus the ability to compensate for such changes islimited.

MIPS has been previously proposed for diagnosis of brain fluidabnormalities. Patents have been awarded for proposed devices, andpromising scientific studies of prototype devices are described in theliterature. For example, Rubinsky et al. described the use of MIPS forthis purpose in U.S. Pat. Nos. 7,638,341, 7,910,374 and 8,101,421, thedisclosures of which are hereby incorporated in their entirety herein(referred to herein as the “Rubinsky Patents”). However, no practical,mass-produced medical device based MIPS technology has yet emerged toprovide clinicians specializing in brain treatment or other areas ofmedicine the promised benefits of such a device.

It was first postulated by Albert Einstein that the velocity of thetransit of electromagnetic radiation in a vacuum is equal to the inverseof the square root of the product of magnetic permeability and electricpermittivity. This formula yields the well-known value of the speed oflight of approximately 3×108 meters/second. The finite time required foran electromagnetic field to propagate through a medium, however, resultsin a time delay, which is manifested as a phase shift (e.g., an offsetor a delay) between a field emitted from a transmitter as compared withthe field as sensed at a receiver. In other words, electromagneticfields typically propagate fastest in a vacuum, and propagate slower ifany matter or medium is present between the transmitter and thereceiver. The amount of slowing is inversely proportional to the squareroot of the product of the relative permeability and relativepermittivity of the medium.

The material makeup of biological materials is almost entirelynon-magnetic, with a relative permeability of approximately 1. Thevariation in the time delay/phase shift through biological materials maytherefore be mainly dependent on the average relative permittivity alongthe path through which the electromagnetic field passes. Relativepermittivity varies for various tissue types and body fluids. Thepermittivity of the biological materials may also depend on thefrequency of a time-varying electromagnetic field and may depend on theambient temperature. The relative permittivity of body fluids is higherthan most brain tissues, and thus, changes in fluid levels in the brainmay have a relatively large effect on the overall phase shift ofelectromagnetic fields as they propagate through a brain or othermedium.

For radiofrequency (“RF”) frequencies below about 200 MHz, the distancebetween opposing sides of the brain is less than one wavelength fornormally propagating transverse electromagnetic waves. This is known asthe near field, and in this region the electromagnetic waves are notfully formed. For this near field magnetic field propagation case, thepropagation time and phase change is predominately determined by theloss factor of the tissues and liquids in the path rather than theirrelative permittivity. The loss factor is a function of the imaginaryportion of the complex permittivity and the conductivity. The physicalmechanism for dissipation of energy is the constant realignment ofpolarized molecules to the changing field polarity. Therefore the lossfactor for a given substance is largely dependent on its ionic content.The ionic content of brain tissue and brain liquids is different foreach substance. When combined with variations in relative permittivity,the various biological tissues and liquids in the brain display uniquephase signatures when looking at phase changes for both the lowerfrequency near field propagation and higher frequency normal propagationcases. Because of the major difference in the physics that causes thephase delay, a multi-spectral measurement using RF frequencies bothbelow and above 200 MHz allows characterization of not only thefractional amount of liquid in the brain, but sub-classifications of theexact nature of the liquid content such as the fractions of blood,cerebrospinal fluid (CSF), or the other liquids that accumulate in thecerebral cavity due to hemorrhaging or edema.

Again, despite research into use of MIPS for diagnosis of fluid changesin the body, no practical medical device based MIPS technology for doingso currently exists. A strong need exists for such technology. Ideally,a medical device solution would provide a MIPS system with improvedperformance, usability and manufacturability, such that it could be usedfor noninvasive fluid change detection in the brain and/or other areasof the body. At least some of these objectives will be addressed by theembodiments described herein.

SUMMARY

Generally, MIPS measurements of electromagnetic fields may be used todetect changes in fluid levels in an area of a body. Detected changes influid levels in various parts of the body may be used to monitor orassess disease states, and in some cases, detected fluid level changesmay be used to determine or adjust a medical or surgical treatment to beadministered to the patient. For example, abnormal fluid changes in thebrain may be used to help determine treatment of abnormalities such asbleeding, edema, or ischemia due to stroke or brain trauma. In otherareas of the body, detection of abnormal fluid level changes may be usedto help treat conditions such as congestive heart failure, lymphedema,and many others.

The present disclosure provides methods and systems to improve theabsolute accuracy of the phase shift measurements and also to therepeatability of phase shift measurements. The present disclosure alsoincludes a more detailed description of the physics of the mechanismthat produces the phase shift, as well as a correlation of phase shiftchanges to the biological processes taking place in brain-injuredpatients. Practical methods are also presented for converting thequantitative phase shift measurement data into a qualitative assessmentof brain health.

Although phase shift is a good way to measure changes to the electricalproperties of tissue that accompany fluid changes, various embodimentsdescribed herein may alternatively use other techniques to measure suchchanges. For example, magnitude changes may be used in some embodimentsto measure changes to electrical properties of tissues. The magnitude ofthe received radiation at the RF detector is affected by the distancefrom the emitter, the geometry and orientation of the emitting andreceiving antennae, and the type and geometry of the various materialsin the path. At lower RF frequencies, the absorption of most biologicalmaterials is quite low. There is significantly more absorption, however,if electrical conductivity or electromagnetic field losses in thematerial is high. The shape and granularity of the materials in theradiation path can cause scattering or refractive lensing, which alsostrongly affects the magnitude of the detected radiation. The change inphase is a more significant effect than the attenuation of themagnitude, and is also easier to decipher. However, the magnitude datamay be useful as a quality check to assure that the emitter and detectorare properly aligned at the time of an individual phase measurement, orfor other purposes. So, while this disclosure will focus primarily onphase shift measurements, various embodiments may alternatively oradditionally employ other techniques.

The disclosure provides a means of measuring phase shift of time-varyingelectromagnetic fields after passing through a patient's brain using anon-invasive, non-contact method. The electromagnetic fields may beproduced by a small transmitter placed on one side of the patient's headthat converts a time-varying input current (for example, asinusoidal-type signal) into a time-varying magnetic field. A smallreceiver or detector placed on the other side of the patient's head maydetect the magnetic field, after passing through the patient's head, andconvert the same to a received time-varying current, in one embodiment.Although the frequency of the received time-varying magnetic field willbe the same as the frequency of the transmitted time-varying magneticfield, there will be a shift in the phase angle between the two fields,which is dependent on the frequency of the signals and the mediumthrough which the magnetic field propagates from the transmitter to thereceiver. In various embodiments, equivalent voltages may be used inplace of currents to measure the magnetic field as transmitted and/or asreceived.

The current in the transmitter and the current in the receiver may besampled by one or more analog to digital (A to D) converters atappropriate sampling rates and intervals determined by a samplingsignal. The conversion from analog electrical signals to digital datamay occur in some embodiments proximate the transmitter and/or receiverlocated near the patient's head. The acquired digital samples of theemitted and received magnetic fields may then be transmitted via digitalsignal busses back to a remote processing unit or processor orprocessing element for processing in some embodiments. In otherembodiments, the analog electrical signals are passed from thetransmitter and receiver through a coaxial cable to an A to D converterin a remote processing unit.

In one embodiment of a diagnostic system for monitoring changes in amedium described herein, the system includes a transmitter configured togenerate and transmit a time-varying magnetic field into a mediumresponsive to a first signal. The system also includes a receiverpositioned on an opposite side of the medium from the transmitter andconfigured to generate a second signal responsive to a received magneticfield at the receiver. The system also includes a processing unitconfigured to determine a phase shift between the transmitted magneticfield and the received magnetic field for a plurality of frequencies ofthe transmitted time-varying magnetic field. At least one of thetransmitter or the receiver includes a loop formed using a shieldedtransmission line.

In some examples, the transmission line may include a first conductor asa shield that at least partially encloses a second conductor, and thesecond conductor provides a signal responsive to a varying magneticfield. The transmission line may include one of a coaxial cable, atwisted shielded pair of wires, a twinaxial cable, or a triaxial cable,and/or the first conductor may form a Faraday cage around the secondconductor. The shielded transmission line may include a strip line on aprinted circuit board coupled between two grounded planes in someexamples, and there may be a plurality of vias between the two groundedplanes. The loop may have a diameter of approximately one inch, may be asingle turn loop, and/or may have a lowest natural resonant frequencyabove 200 MHz. In some examples, the loop may be a first loop positionedin a first layer of a printed circuit board, and the system may furtherinclude a second loop positioned in a second layer of the printedcircuit board and formed using strip line, with leads from both thefirst and second loops are coupled to a differential amplifier. Theprinted circuit board may also include a plurality of grounded shieldingplanes positioned above and below the loop in the printed circuit board.The grounded shielding planes may each define a circular void, with aninternal diameter of the circular void being smaller than an internaldiameter of the loop. A balun may be coupled to the loop and configuredto balance the output of the loop, and/or the output of the loop may bebalanced to effectively have a 50 ohm output impedance.

Also, in some examples, the system may include a first analog to digitalconverter coupled to the transmitter and positioned proximate thetransmitter, and also may include second analog to digital convertercoupled to the receiver and positioned proximate the receiver. The firstanalog to digital converter and the transmitter may be coupled to asingle printed circuit board. The processing unit may include a samplingsignal generator configured to generate a sampling signal, the samplingsignal having a frequency to under-sample the transmitted and receivedmagnetic fields. The processing unit may further be configured toaverage a plurality of respective samples of the transmitted andreceived magnetic fields and determine the phase shift between theaveraged transmitted magnetic fields and the averaged received magneticfields. The processing unit may include a sampling signal generatorconfigured to generate a sampling signal, with the sampling signal beingsuch so as to coherently sample the transmitted and received magneticfields. The processing unit may further be configured to calculate afast Fourier transform of samples of the transmitted and receivedmagnetic fields, and determine the phase shift by comparing the phasecomponents of the calculated respective fast Fourier transforms.

In some examples, the transmitter may be a first transmitter and thetime-varying magnetic field may be a first time-varying magnetic field,and the system may further include a second transmitter also configuredto generate and transmit a second time-varying magnetic field into themedium responsive to a third signal, the second transmitter being offsetfrom the first transmitter. A first frequency of the first time-varyingmagnetic field generated and transmitted by the first transmitter may bedifferent from a second frequency of the second time-varying magneticfield generated and transmitted by the second transmitter. In someexamples, the receiver may be a first receiver, and the system mayfurther include a second receiver configured to generate a third signalresponsive to a received magnetic field at the second receiver, thesecond receiver being offset from the first receiver. The processingunit may be configured to triangulate the location of a change in fluidresponsive to the received magnetic field at the first and secondreceivers.

In some examples, the processing unit may be configured to reduce errorsin the determined phase shift resulting from movement of thetransmitter, the receiver, or a patient. The system may include anaccelerometer coupled to the transmitter or to the receiver, and theprocessing unit may exclude data corresponding to periods of timewherein the accelerometer detects significant motion of the transmitteror receiver. The processing unit may exclude data corresponding toperiods of time during which the determined phase shift between thetransmitted magnetic field and the received magnetic field is such thatit is unlikely the result of biological changes within the medium. Theprocessing unit may further be configured to initialize the diagnosticsystem responsive to an air scan.

In some examples, the receiver may be a first receiver, and the systemmay further include a second receiver positioned proximate thetransmitter and configured to generate a third signal responsive to thetransmitted magnetic field and indicative of the phase of the magneticfield proximate the transmitter. The second receiver may be concentricwithin the first receiver.

In some examples the processing unit may include a first FPGA configuredto synthesize the first signal, a second FPGA configured to collect andaverage a first plurality of samples from the second signal and a secondplurality of samples representative of the phase of the transmittedmagnetic field, a third FPGA configured to determine a phase measurementbased on the averaged first and second plurality of samples, and amicrocontroller coupled to the first, second, and third FPGAs andconfigured to control the first, second, and third FPGAs.

In another embodiment of a diagnostic system for monitoring fluidchanges in a patient described herein, the system may include a headsetand a transmitter coupled with the headset and configured to generateand transmit a time-varying magnetic field into the patient responsiveto a first signal. A receiver is also coupled with the headset such thatit is located on approximately an opposite side of the patient's headfrom the transmitter when the headset is applied to the patient's headand configured to generate a second signal responsive to a receivedmagnetic field at the receiver. At least one spacer is disposed betweenthe transmitter and the patient's head and the receiver and thepatient's, and a processing unit is configured to determine a phaseshift between the transmitted magnetic field and the received magneticfield for a plurality of frequencies of the transmitted time-varyingmagnetic field.

In some examples, the headset may include an elastic headband, and thesystem may also include stabilizers that couple the transmitter andreceiver to the patient's head. The stabilizers may be moldable to thepatient's head to hold the transmitter and receiver in place, and thespacers may be plastic disks.

In another embodiment of a method for monitoring intracranial fluid in apatient described herein, the method includes transmitting a firsttime-varying magnetic field from a transmitter toward a receiver,wherein the transmitter and the receiver are coupled to approximatelyopposite sides of the patient's head via a headset, and wherein at leastone spacer is disposed between each of the transmitter and the patient'shead and the receiver and the patient's head. The method also includesreceiving the first magnetic field with the receiver, and determining abaseline phase shift between the transmitted magnetic field and thereceived magnetic field for a plurality of frequencies of thetransmitted time-varying magnetic field. The method also includestransmitting, at some time after the first time-varying magnetic fieldis transmitted, a second time-varying magnetic field from thetransmitter toward the receiver, receiving the second magnetic fieldwith the receiver, and determining a new phase shift between thetransmitted magnetic field and the received magnetic field for aplurality of frequencies of the transmitted time-varying magnetic field.The method also includes comparing, with a processor coupled with theheadset, the new phase shift to the baseline phase shift, determining,using the processor and based on the comparison between the new andbaseline phase shifts, whether a clinically significant change inintracranial fluid has occurred, and generating a signal, via theprocessor, if it is determined that the clinically significant changehas occurred.

In some examples, the method may also include converting the receivedmagnetic fields with an analog to digital converter coupled directlywith the headset at or near the receiver, and may also includeconverting the transmitted magnetic fields with an analog to digitalconverter coupled directly with the headset at or near the transmitter.Generating the signal may include triggering an alarm.

In some examples, the first and second magnetic fields are in afrequency range of about 20 MHz to about 300 MHz. Also, the method mayinclude, before transmitting the first time-varying magnetic field,initiating the headset by transmitting a calibration magnetic field fromthe transmitter to the receiver while the headset is not coupled withthe patient. At least one of the transmitter or the receiver may includea loop formed using strip line on a printed circuit board, wherein theloop has a diameter of approximately one inch and is a single turn loop.

In some examples, the method may further include detecting motion of thepatient with a motion detection member, transmitting a signal to theprocessor based on the detected motion, and distinguishing, using theprocessor, the comparison of the new and baseline phase shifts from thedetected motion of the patient.

In some examples, the method may further include calculating, with theprocessor, a fast Fourier transform of samples of the transmitted andreceived magnetic fields, and determining the first and second phaseshifts by comparing phase components of the calculated respective fastFourier transforms. In some examples, coupling the headset with thepatient's head may include positioning an elastic headband on the head,wherein the transmitter and the receiver are mounted to the elasticheadband, and wherein a spacer is coupled with each of the transmitterand receiver so as to be disposed between the transmitter and receiverand the patient's head when the headband is positioned on the head.

In some examples, the steps of the method may be repeated multiple timesover time to monitor the fluid over time. The method may also includerecommending a treatment, based on the generation of the signal, and thetreatment may be an amount of mannitol to be delivered to the patient toreduce an amount of intracranial fluid.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of a system for monitoring fluid changes inthe body, according to one embodiment;

FIG. 1A is a perspective view of a patient headpiece for use in thesystem of FIG. 1, according to one embodiment;

FIG. 1B is a perspective exploded view of another patient headpiece foruse in the system of FIG. 1, according to one embodiment;

FIGS. 2A through 2F illustrate various embodiments of transmittertransducers and receiver sensors for use in the system of FIG. 1;

FIG. 3 is a circuit diagram of a phase shift detection apparatus,according to one embodiment;

FIG. 4 is a simplified logic diagram for a waveform averager processorfor use in the system of FIG. 1, according to one embodiment;

FIG. 5 is a simplified logic diagram of a phase shift measurementprocessor for use in the system of FIG. 1, according to one embodiment;and

FIG. 6 is a flow diagram for the operation of the system of FIG. 1,according to one embodiment.

DETAILED DESCRIPTION

Certain details are set forth below to provide a sufficientunderstanding of certain embodiments of the present disclosure. However,some embodiments of the disclosure may be practiced without theseparticular details. Moreover, the particular embodiments of the presentdisclosure are provided by way of example and should not be used tolimit the scope of this disclosure to those particular embodiments. Insome instances, well-known circuits, control signals, timing protocols,and software operations have not been shown in detail in order to avoidunnecessarily complicating the description.

Overall System Architecture

FIG. 1 is a block diagram of one embodiment of a system 100 that may beused to detect fluid changes in a human brain. Although this descriptionoften focuses on use of the system 100 for detecting fluid changes inthe brain, this embodiment of the system 100 or alternative embodimentsmay be used for detecting/monitoring fluid changes in any other part ofthe body. Therefore, the exemplary description provided herein that isdirected toward the brain should not be interpreted as limiting thescope of the invention as it is set forth in the claims.

The system 100 may include a laptop computer 102, a processing unit 104,and a patient headpiece 106 in some examples. The system 100 may becontrolled, for example, by a Windows-based LabView language programrunning on the laptop computer 102. The program generates a graphicaluser interface (GUI) that is displayed on the screen of the laptop 102.The clinician who operates the system 100 may initiate monitoring bymouse control after placing the headpiece 106 on the patient, which maybe similar to an elastic headband or bandage. After initiation ofmonitoring, the program may run unattended as it logs the phase shiftdata on the laptop 102 and applies the appropriate methods to generatealarms and suggested corrective actions to a clinician.

The laptop 102 may have a USB serial link to the processing unit 104.This USB link may be electrically isolated to conform to applicablemedical device requirements. The processing unit 104 may derive powerfrom a standard universal AC line power connection consistent withinternational standards. There may be a medical grade low-voltage DCpower supply to power all of the processing unit's 104 internalelectronics that meets applicable standards for patient isolation, lineto neutral, chassis, and patient leakage as well as earth to groundcontinuity, EMI susceptibility and emissions, and other standard medicaldevice requirements.

The laptop 102 may initiate phase shift data collection and log the datain files on the laptop's 102 hard drive along with other pertinent dataand status information.

The GUI on the laptop 102 may control the operation of the system 100,and may include controls and status indications that guide the clinicianthrough installation of the patient headpiece 106 and a preliminaryself-test of the entire system 100. If the self-test passes, theclinician is instructed to initiate monitoring. During monitoring, thephase shift angle versus frequency data is collected from the USBinterface and appropriate status and alert methods are applied to thedata. The clinician may be informed if additional actions or emergencyresponses are indicated. The phase shift versus frequency data andadditional status information is logged in the laptop 102 for laterreference. A “sanity check” of the data and other built-in-test featuresmay run continuously in the background, and if a fault is encountered,various levels of severity will generate warnings or interrupt operationof the system 100.

The architecture of hardware and firmware in the processing unit 104 andthe patient headpiece 106 may be optimized to achieve the desired phasemeasurement accuracy and stability while using a minimum number ofcustom electronics components in some examples and as illustrated inFIG. 1. For example, in one embodiment, and with reference to FIG. 1,the system 100 may comprise several highly integrated miniaturizedoff-the-shelf components. The system 100 may include three fieldprogrammable gate arrays (FPGAs) 110, 112, 114 in the processing unit104, the three FPGAs being programmed with appropriate firmware. OneFPGA 110 may synthesize a time-varying signal to be provided to atransmitter 120 to generate a magnetic field, the second FPGA 112 maycollect and average digital samples of transmitted and received magneticfields, and the third FPGA 114 may measure the phase shift between thetransmitted and received signals representative of the transmitted andreceived magnetic fields.

A microcontroller 118 may also be included in the processing unit 104,and may supervise the actions of the three FPGAs 110, 112, 114 andcommunicate with the laptop 102 (e.g., by transferring phase dataresults). The microcontroller 118 may provide an interface between theexternal laptop computer 102 (via an electrically isolated USBinterface) and the FPGAs 110, 112, 114 used for real time signalprocessing of the data from the headpiece 106. The microcontroller 118may also perform other miscellaneous functions such as the interface tobasic user controls including power-on, initiation of data collection,setup of the frequency synthesizer 110, internal temperature monitoring,power supply monitoring, and other system status monitoring and faultdetection tasks.

The processing unit 104 may in some examples be fabricated from larger,integrated components. In one embodiment, the processing unit 104 mayinclude an off-the-shelf electronic signal generator, such as aTechtronix Arbitrary Waveform Generator model 3252, and a digitaloscilloscope such as LeCroy Model 44xi.

The architecture of the system 100 illustrated in FIG. 1 may berelatively flexible, allowing improvements in all phases of the datacollection, data processing, and data interpretation (e.g., clinicalalerts) to be made through relatively simple software or firmwaremodifications. The FPGAs 110, 112, 114 may effectively function asparallel processors to make data collection and processing proceed innear real time. The quantity of phase data transmitted via themicrocontroller 118 to the laptop 102 and archived for later referencemay thus be reduced, thereby requiring less computation time on thelaptop 102 for processing the data. This may in turn free up the laptop102 for checking data consistency and applying methods required foralerting clinicians to the need for corrective actions.

Although the processing unit 104 in FIG. 1 has been illustrated anddescribed as a relatively flexible embodiment, in other examples thediagnostic system 100 may be an embedded system with custom electronicscomponents specially designed for use in the diagnostic system 100. Forexample, one or more A to D converters may be located in the processingunit 104, which may be physically distinct and separate from theheadpiece 106, or which may be integral with the headpiece 106 (e.g.,the headpiece 106 may, in a custom system 100, include all of theelectronics and processing equipment needed to capture and process phaseshift information). In general, any suitable architecture may be used.

Referring again back to FIG. 1, the system 100 may also include aheadpiece 106 with one or more transmitters 120 and one or morereceivers 124, the details of which are explained in more detail below.In one example, the headpiece 106 includes a single transmitter 120 anda single receiver 124, whereas in other examples, the headpiece 106includes several transmitters 120 and/or several receivers 124. Forexample, the headpiece 106 may include one transmitter 120 and tworeceivers 124. If multiple receivers 124 are placed at differentpositions over a patient's head, they may allow a clinician totriangulate the location of a fluid change (e.g., intracerebral bleedingfrom a blood vessel or tumor) and/or image the biological impedance of apatient's brain. In other examples, the headpiece 106 may includemultiple transmitters 120, which may produce magnetic fields atdifferent or similar frequencies. If different frequencies are used, asingle or multiple receivers 124 may be able to distinguish among theseveral transmitted frequencies in order to, for example, furtherdistinguish the type of fluid change.

In some examples, in addition to the receiver 124 positioned elsewhereon the patient's head, an additional receiver may be positioned on thesame side of the patient's head as the transmitter 120 (e.g., thereceiver may be concentric within or may circumscribe the transmitter120, or may be positioned in a separate plane from the transmitter 120)in order to obtain a measurement of the transmitted magnetic field fromthe transmitter (not shown in FIG. 1). In other examples, the emittedmagnetic field may be sampled from the transmitter 120 in anotherfashion, such as by measuring the current and/or voltage present on thetransmitter 120. In some examples, and with reference to FIG. 1, thepatient headpiece 106 includes A to D converters 122, 126 for one ormore of the transmitter(s) 120 and/or receiver(s) 124 proximate therespective transmitter(s) 120 and/or receiver(s) 124 themselves—forexample, A to D converters may be positioned on the same printed circuitboard as the respective transmitters 120 or receivers 124 in someexamples.

In other examples, however, the analog signals are not converted intodigital signals until after being passed through one or more coaxialcables (or other transmission lines) connected to a separate processingunit (e.g., the processing unit 104 shown in FIG. 1). In these examples,various techniques may be employed to reduce cross-coupling between, forexample, a coaxial cable carrying a signal indicative of the transmittedmagnetic field from the transmitter 120 and a coaxial cable carrying asignal indicative of the measured magnetic field from the receiver 124.For example, a relatively flexible RF-316 double shielded cable may beused to increase the isolation between the two cables, or, in otherexamples, triple shielded cables may be used. As another option, highlyflexible PVC or silicone tubing may be provided around the coaxial cablefrom the receiver 124 and/or transmitter 120.

Referring again to the headpiece 106 illustrated in FIG. 1, forrepeatable readings, it may be important for the transmitter 120 andreceiver 124 to not move during operation of the system 100 because suchmovement may introduce an error in the phase shift measurement. In orderto overcome such errors, the transmitter 120 and receiver 124 may bemounted in a rigid manner in some examples, for example in an apparatusthat resembles a helmet 140, one example of which is illustrated as FIG.1A. The helmet 140 may provide the necessary support and rigidity toensure that the transmitter 120 and receiver 124 remain fixed relativeto each other and relative to the patient's head. However, such a helmet140 may be uncomfortable or impractical to use on a patient while theyare lying down. Also, it may not be practical for a patient to wear thehelmet 140 for several days as may be desirable in some clinicalsituations.

Accordingly, in an alternate embodiment, and with reference to FIG. 1B,the transmitter 120 and receiver 124 are held against the head of thepatient using a headset 129, such as an elastic band 129. Thetransmitter 120 and receiver 124 may be mounted on the headset 129, forexample, by securing them inside a pocket of the headset 129, or usingstitches, rivets or other fasteners. The transmitter 120 and receiver124 may be spaced at a fixed distance from the surface of the skin byincorporating a non-conductive spacer material 127, such as plastic orfabric. The spacers 127 can serve the purpose of maintaining a fixeddistance between the transmitter 120 and receiver 124 from the skin inorder to, for example, reduce variability of the capacitance between thetransmitter 120/receiver 124 and the skin. The spacers 127 may be, forexample plastic acrylic disks in some embodiments. Rubber, medicaladhesive, or other material may also or alternatively be used for thespacers 127, and may be placed at the skin interface surface of thetransmitter 120 and receiver 124 to aid in keeping them from movingduring use. The headset 129 may be placed on the patient's head acrossthe forehead and around the back of the head in some embodiments; or adifferent band or other device can be placed in other configurations,including around a patient's arm or leg. In other words, any suitablepositioning device may be used to appropriately position the transmitter120 and receiver 124 proximate the area of the patient's body underinvestigation, of which the headsets 106, 129 and headbands 129described herein are merely examples. Additional features such as a chinstrap or a connection over the top of the head can be added to theheadset 129 to provide additional stability and to provide features onwhich to mount additional transmitters 120 or receivers 124. Since thepatient will often be lying on a pillow, a convenient location forelectrical components and for cable terminations might be the top of thehead. For example, a bridge from a point near each ear may be created sothat the electronics can be mounted at the top of the head, away fromthe surfaces that the patient may lie on. Low-profile components thatare lightweight may be used so as to maximize comfort and minimize thetendency of the headset to move on the patient's head once in place.

In the headset 129 design, a headband 129 may be made of elastic,rubber, acrylic, latex or other flexible material, and may be elastic orinelastic. The headset 129 may be fabricated from inexpensive materialsso the headset can be a disposable component of the system.Alternatively, the headset 129 may be reusable. If it is reusable, theband 129 may be washable so that it can be cleaned between patients, orcleaned periodically for the same patient. Washable materials mayinclude plastic, rubber, silicone, fabric, or other materials. Theheadpiece 106 may also include mounting means for securing theelectronic components and to route the cables to keep them from gettingin the way of the patient or the clinical staff.

In some embodiments, including those where a headband 129 is used, inorder to reduce the relative motion between the transmitter 120/receiver124 and the patient, one or more stabilizers 128 may be used.Stabilizers 128 may be custom-molded to the patient's body to hold thetransmitter 120 and/or receiver 124 in place. As one example of astabilizer 128, trained clinicians may install the transmitter120/receiver 124 using low-melting-point plastic that is similar toorthopedic casts made from the same material. Other custom-shapeablematerials and methods may be used, such as materials which polymerizeover time, or with activation by heat or chemical reaction such asmaterials used for making orthopedic casts or splints.

With reference now to the exploded view of FIG. 1B, the operation of oneembodiment of using a headset 129 will be described, although it will beunderstood that similar bands 129 may be used to monitor fluid change inother parts of the body, such as a bandage wrapped around a leg or anarm. Each transmitter 120/receiver 124 may first be coupled to arespective spacer 127 by, for example, a screw or other fastener such asglue. The transmitter 120 and respective spacer 127 may then bepositioned on a patient's head, and the stabilizer 128 may be positionedaround the transmitter 120/spacer 127 in order to stabilize thetransmitter and help prevent movement. The stabilizer 128 may need to besoaked in water or otherwise prepared for application prior topositioning it around the transmitter 120/spacer 127. Once thestabilizer 128 secures the transmitter 120/spacer 127, anotherstabilizer 128 may similarly be used to stabilize the receiver 124 andspacer 127 in a similar manner. The stabilizers 128 may solidify or dryout to perform the stabilizing function. Then, a headset such as aheadband 129 may be wrapped around the stabilizers 128 and transmitter120/spacer 127 and the receiver 124/spacer 127. In some embodiments,however, no stabilizers may be used, and the headband 129 may instead beused to directly position the receiver 124/spacer 127 and thetransmitter 120/spacer 128 on the patient's head. In still otherembodiments, and as mentioned above, the headband 129 may includepockets for the transmitter 120 and receiver 124, with the headband 129material itself acting as a spacer. Also, in some embodiments, theheadband 129 may have non-slip material applied to an interior side ofthe headband 129 to help prevent slippage of the headband 129 on thepatient's head.

The apparatus and methods described herein may be used, in variousembodiments, for fluid measurement (often fluid change measurement) inall parts of the body and for multiple medical diagnostic applications.The configuration of the emitter and detector coils may be modified, invarious embodiments, to be appropriate to the area of the body and/orthe diagnostic application involved. For example, for an applicationinvolving a limb, such as the arm, or where it may be more important tomeasure liquid content at a shallow depth in the tissue, the emittercoil and detector coil may be placed on the same side of the subjecttissue. A co-planar arrangement may be appropriate. Since the coils maybe separated by a much shorter distance, the received signal strengthmay be much greater, and the size of the coils may be reduced. Invarious alternative embodiments, the coils may be in a side-by-sideco-planar arrangement or in a concentric co-planar arrangement usingcoils with different diameters. In some embodiments, it may be moreappropriate to place the plane of the coils at a slight angle to conformto the shape of the body part under study.

With reference now to FIG. 6, one example of the operation of the system100 will now be briefly described, it being understood that variousoperations illustrated in FIG. 6 will be described in more detail below,and various alternative methods and modes of operation will also bedescribed below. Beginning at operation 501, the system 100 is poweredon and a self-test is performed. If the system 100 fails the test, astop or fail indicator is displayed on the laptop 102 in operation 502.If the system 100 passes the power-on self-test, operation moves tooperation 504. Also, throughout operation of the system 100, acontinuous status monitor may run in operation 503, and, should thestatus monitor determine that system 100 is failing, the system maydisplay a stop or fail indicator in operation 502.

Once the system 100 passes the power-on self-test and operation hasmoved to operation 504, the frequency synthesis FPGA 110 may beinitialized and begin to provide the transmitter 120 with the transmitsignal in operation 504. The waveform averager FPGA 112 may begin tocollect and average waveforms from the transmitter 120 and the receiver124 in operation 505. The averaged waveforms may be provided to thephase shift measurement FPGA 114, which may determine the phase shiftbetween the transmitter 120 and receiver 124 waveforms beginning inoperation 506, with the ultimate phase calculation of interest beingcalculated in operation 507. The phase calculation may be provided tothe laptop 102 in operation 508. At any point after operation 505, thefrequency synthesizer FPGA 110 may provide another frequency to thetransmitter 120, and the process may repeat for the next frequency.Multiple frequencies may thus be emitted from the transmitter 120 andsubsequent phase shifts calculated. For example, the frequency synthesisFPGA 110 may provide the next frequency in repeated operation 504 whilethe phase shift measurement FPGA 114 measures the phase shift betweenthe waveforms from the previous frequency, or the frequency synthesisFPGA may not provide the second frequency until the phase calculationhas been provided to the laptop in operation 508. In an alternateembodiment, the emitter can emit a single frequency simultaneously withharmonic frequencies, or through the use of multiple frequencygenerators, for later separation using techniques such as Fast FourierTransform (FFT). Simultaneous emission of multiple frequencies can beadvantageous for noise cancellation, motion rejection and otherpurposes.

The Transmitter(s) and Receiver(s)

One range of electromagnetic frequencies appropriate for an inductivephase shift measurement based system 100 for brain fluid diagnostics isin the radio frequency (RF) range from about 20 MHz to 300 MHz, althoughother frequencies may also be used, such as between 1 MHz and 500 MHz,between 3 MHz and 300 MHz, and so forth. The frequencies chosen mayprovide relatively low absorption rates in human tissues, good signalrelative to noise factors, such as capacitive coupling and signal linecross-talk, and ease of making accurate phase measurements.

Previously, certain examples of transmitters (and correspondingreceivers) that emit (and sense) magnetic fields in these frequencyranges were constructed of thin inductive coils of a few circular turnsplaced such that the plane of the coil is parallel to the circumferenceof the head. (See, for example, the Rubinsky Patents, previouslyincorporated herein by reference.) The coils of these previoustransmitters and receivers had diameters of 10 cm or more and 5 or moreturns. These relatively large transmitter and receiver coils, however,were cumbersome and furthermore had resonances within the range of thefrequencies of interest for MIPS detection of fluid in a human brain.When transmitter or receiver coils are operating in a frequency near oneof their natural resonant frequencies, a measured phase shift may belargely a function of the magnitude of the coil's own parasiticcapacitances, and very small changes due to motion of either of thecoils and/or environmental effects can cause large changes in the phaseshift, creating unacceptable noise in the measurement of phase shift.

Accordingly, in some embodiments of the present disclosure, the lowestnatural resonant frequency of the transmitter 120 and/or receiver 124may be higher than the intended frequencies of the magnetic fields to betransmitted. In some examples, the transmitter 120 may include a coil asa magnetic field generator or transducer. From symmetry considerations,this same or a similar coil may act as a magnetic field sensor in areceiver 124. In either case, as the diameter of the coil and number ofturns (i.e., loops) is reduced the first self-resonant frequencygenerally increases. The limit, therefore, is for a coil with a singleloop, the loop having a very small diameter. As the loop diameterdecreases, however, the amount of magnetic flux intercepted by the loopis reduced by a factor equal to the ratio of diameters squared.Likewise, the induced voltage in the loop is reduced, resulting in asmaller signal from a loop acting as a magnetic field sensor in areceiver 124. Thus, there are practical limits on the diameterreduction. In some embodiments, however, an additional increase in theself-resonant frequency can be achieved by using transmission linetechniques in the construction of the transmitter 120/receiver 124.

An alternative to using coils designed for a relatively constant phaseshift over a wide bandwidth is to add external reactive components in aseries-parallel network to tune out the phase shift at a singlefrequency or at a small number of discrete frequencies. This conceptworks best if the approximate value of the individual frequencies isknown prior to designing the overall system and the number of discretefrequencies is small. By using switched or motor driven tunablecomponents, the phase shift tuning can be automated and softwarecontrolled. An advantage of tuning to a constant phase shift is that itprovides more freedom in the choice of the size and shape of the coils.Using larger coils can increase the detected signal strength and providea field shape that is optimally matched to the portion of the brain orother body part that is being sampled.

In one embodiment, with reference to FIG. 2A, a single loop 250 with ahigh self-resonant frequency and associated stable phase response belowthe self-resonant frequency may be constructed using a shieldedtransmission line, such as coaxial cable, buried strip-line on a printedcircuit board, a twisted shielded pair of wires, a twinaxial cable, or atriaxial cable. The loop 250 may be used as either a magnetic fieldgenerator in the transmitter 120 or as a magnetic field sensor in thereceiver 124. The shielded transmission line may include a firstconductor as a shield 251 that at least partially encloses a secondconductor. The first conductor or shield 251 may be grounded and mayform a Faraday cage around the second conductor. The second conductormay provide an output signal responsive to the changing magnetic field,and, due to the Faraday cage, the second conductor may be shielded fromexternal electrostatic effects and from capacitive coupling. Forexample, in one embodiment, a single loop 250 of buried strip line maybe sandwiched between two grounded planes in a printed circuit board. Aplurality of vias may extend between the two grounded planes, with thespacing of the vias determined by the wavelengths of the electromagneticfield being transmitted and/or received, and the vias together with thetwo grounded planes forming an effective electrostatic or Faraday cagearound the buried strip line loop 250. In other embodiments, other typesof transmission lines with an outer shield (such as coaxial cable) maybe used in order to form a Faraday cage and thus reduce externalelectrostatic effects on the loop 250.

In single loop 250 embodiments of a transmitter 120 or receiver 124, thevoltage of the loop 250 may not be in phase with the current of the loop250 due to the inductive nature of the single loop 250. This phase errormay be detected and accounted for during initialization of thediagnostic system 100, as described below. In some embodiments of thesingle transmitter loop 250, however, and with Reference to FIG. 2B, abalun transformer 254 may be added, in order to obviate the need tocorrect for this phase error. In still other embodiments, and withreference to FIG. 2C, a second, independent, smaller, concentric loop260 is used to sense the transmitted magnetic field and provide acurrent representative of the same to the A to D converter. The second,concentric transmitter loop 260 may in some examples be the same size asthe corresponding receiver loop (e.g., in receiver 124) in order to haveproportional signals and good uniformity between them, whereas in otherexamples the receiver loop may be larger than the second, concentrictransmitter loop 260 in order to be more sensitive to the receivedmagnetic field. In those transmitters 120 with the second, concentrictransmitter loop 260, and with reference to FIG. 2D, a balun transformer264 may likewise be used on this second, concentric loop 260 in order tobalance the sensed voltage and current. Furthermore, for a single-turnreceiver loop 250, a balun 254 may likewise be added in order to alsobalance its performance, similar to that shown for the transmitter cablein FIG. 2B.

Referring now to FIG. 2E, in another embodiment, the transmission lineconcept may be extended from building a single-loop, single-ended deviceto building a dual-loop 270, which may be double-ended or “balanced,”for use as a receiver 124 (or, symmetrically, for use as a balancedtransmitter 120). In FIG. 2E, four conductive (e.g., copper) layers 271,272, 273, 274 may be formed on a printed circuit board as shown, withthree layers of dielectric material (not shown in FIG. 2E) coupledbetween the four conductive layers 271, 272, 273, 274 when stackedvertically. The top and bottom layers 271, 274 may be grounded and thusform an electric shield. Furthermore, small linear breaks 271 a, 274 amay be present in both of the top and bottom layers 271, 274 so that theground planes 271, 274 don't act like additional shorted turns. Inbetween the top and bottom ground layers 271, 274, the +loop 273 and the−loop 272 may be positioned, with the leads from the two loops 272, 273being coupled to a balanced amplifier (not shown in FIG. 2E). The +loop273 and the −loop 272 may be center tapped in some examples. The innerdiameter of the two loops 272, 273 may be approximately 1 inch, and maybe slightly greater than the inner diameter of the circular void in thetwo grounded planes 271, 274. In some embodiments, the thickness andpermittivity of the dielectric material, the width and thickness of theconductive material forming the loops 272, 273, the spacing of theground planes 271, 274, and so forth, may be chosen such that the doubleloop 270 has approximately a 50 ohm impedance in order to match thetransmission line to which it will be coupled. In this manner, theself-resonant frequency of the dual loop structure 270 may be above 200MHz in some examples.

Still with reference to FIG. 2E, for a dual loop 270 used as a magneticfield sensor in a receiver 124, external noise that is coupled into thesystem 100 from environmental changes in the magnetic field due toenvironmental EMI sources or motion of nearby conductors or magneticmaterials may be reduced due to the common-mode rejection of thedifferential amplifier to which the two loops 272, 273 are coupled.Having the differential amplifier coupled to the loops 272, 273 whenused as a receiver 124 thus may allow the loops' 272, 273 diameters tobe reduced while keeping the output signal level at a suitable level fortransmission to a remote processing unit 104 (e.g., for those systemswhere one or more A to D converters are not located directly in theheadpiece 106). The amplifier power gain may be approximately 40db insome embodiments. Low-cost wide-bandwidth amplifiers offering gains of40db for the power levels of interest are readily available inminiaturized packages from multiple suppliers with negligible phaseshift variation over a 20 MHz to 200 MHz frequency range.

With reference to FIG. 2F, as suggested, the dual loop 270 used for abalanced receiver 124 has an analogous application as a magnetic fieldgenerating transmitter 120. The balanced approach for constructing atransmitter 120 may result in a common-mode cancellation of noise in thetransmitted magnetic field due to the opposite winding directions of thedual loops, thus reducing noise in the transmitted magnetic field thatmay otherwise result from electrostatic or magnetic pickup fromenvironmental factors.

Referring still to FIGS. 2E and 2F, in some embodiments, the two loops272, 273 may be formed in different planes, or, in other embodiments,the two loops may be fabricated in the same plane with concentriccircular strip-line traces (thus reducing the number of layers requiredin fabricating the PC board). This concentric design may be used for thetransmitter 120, and/or the receiver 124.

Also, with reference to any of FIGS. 2A through 2F, in examples wherethe analog to digital conversion is not done proximate the transmitter120 or receiver 124, a resistive attenuator may be added to the PC boardwith surface-mount resistors in order to help reduce cross-coupling ofthe transmitter signal to the receiver signal in the cable through whichthe analog signals are transmitted, which may help increase phasemeasurement accuracy and stability. The on-board attenuator may resultin a substantial size and cost reduction compared with a bulky separatemodular attenuator. Also, still continuing with examples where theanalog to digital conversion is not done proximate the transmitter 120or receiver 124, with reference still to any of FIGS. 2A through 2F, oneor more amplifiers may be provided to amplify the signals from thetransmitter 120 and/or the receiver 124 in order to reduce attenuationof the signals through the cable to the external analog to digitalconverter 122, 126. Still continuing with examples where the analog todigital conversion is not done proximate the transmitter 120 or receiver124, the voltage on the transmitters and receivers may be in phase withcurrent on the respective transmitters and receivers because the“balanced” transmitter and receivers illustrated in FIGS. 2E and 2F areterminated in the 50 ohm characteristic impedance of coaxial line.

Referring now to FIG. 3, an alternative design may include an amplifier256 on the same printed circuit board as the loop 250. Including anamplifier 256 on the same printed circuit board as the loop 250 (that isused, for example, as a receiver 124) may help increase the signal tonoise ratio, which may be particularly useful for embodiments whereanalog to digital conversion is done remotely from the headpiece 106. Anamplifier 256 may also be used in embodiments where analog to digitalconversion of a signal is done near the loop 250. As mentioned above, abalun transformer (not shown in FIG. 3) may be also included on theprinted circuit board between loop 250 and the amplifier 256, which mayhelp cause the coil to operate in a “balanced” mode. In the balancedmode, capacitively coupled electromagnetic interference pickup or motioninduced fluctuations in the signal level may be reduced or canceled,since they typically equally couple into both the negative and positiveleads of the balanced differential signal.

Initialization: Air-Scan to Remove Fixed-Phase Errors

As suggested above, the diagnostic system 100 may be initialized in someexamples in order to calibrate the transmitter 120 individually, thereceiver 124 individually, the transmitter 120 and the receiver 124 withone another and with the other associated electronics, and so forth. Forexample, variations in lead lengths and amplifier time delays in signalpaths from the transmitter 120 and receiver 124 may be detected duringinitialization and removed from the signals during signal processing inorder to prevent fixed offset errors in the data. Also, any phase shiftbetween (measured) voltages and currents in a single-turn loop 250 maybe detected.

The initialization may in one embodiment be an “air-scan” where thetransmitter(s) 120 and receiver(s) 124 are positioned with only airbetween them, the transmitter(s) 120 and receiver(s) 124 positionedapproximately as far apart as they would be if they were positioned onthe head of an average patient. Once thus spaced, phase shift data iscollected for a range of different frequencies (because the errors maybe constant across or varying among different frequencies), and thecollected air-scan values may be subsequently used during signalprocessing to correct any phase shift errors of the system 100 (e.g., bysubtracting them from the values obtained during operation of the system100). The initialization may be done when the A to D converters 122, 126are in the headpiece 106 proximate to the transmitter 120 and receiver124, when the A to D converters 122, 126 are external to the headpiece106, and so forth.

Generation of the Driving and Sampling Signals

As mentioned above, the diagnostic system 100 collects phase shift datafor transmitted time-varying magnetic fields at multiple frequenciesbecause the phase shifts contributed by various tissue types and bodyfluids may vary with frequency. The diagnostic system 100 illustrated inFIG. 1 provides a flexible frequency synthesizer 110 within theprocessing unit 104, although in other embodiments, a frequencysynthesizer 110 may be provided in, for example, the headpiece 106. Thisfrequency synthesizer 110 may have a minimum of 1 MHz resolution overthe range of about 20 MHz to 200 MHz in some examples (or alternativelyabout 20 MHz to 300 MHz or about 10 MHz to 300 MHz or any of a number ofother suitable ranges). Standard digital phase-lock loop techniques maybe used to derive the selectable frequencies from a single stablecrystal-controlled clock oscillator. As described above, the digitalportions of the synthesizer 110 may be implemented in one of the FPGAs110 in the processing unit 104. The synthesizer 110 may produce both abasic square wave clock signal for generating the magnetic field in thetransmitter 120 as well a sampling signal. The sampling signal may be ata slight offset (e.g. 10 KHz) in frequency from the magnetic fieldgenerating signal in some embodiments. The square wave signal forgenerating the magnetic field may, in some embodiments, be amplified tocorrect its level and may also be filtered to eliminate higher orderharmonics and achieve a low distortion sine wave at one or morefundamental frequencies.

In other cases, where frequency domain techniques such as FFT processingof the time domain data are used to calculate phase, it may beadvantageous to accentuate the harmonics of the fundamental frequency.For these embodiments, additional circuits may be added after the basicfrequency synthesizer to make the rise-time or fall-time of asquare-wave or pulse wave-shape much faster, thereby increasing therelative amplitude and number of higher order harmonics. As mentionedpreviously, this embodiment allows generation of a “comb” of frequencieswith a single burst of RF and the processing of the captured time domaindata from the emitter and detector using Fourier techniques yields asimultaneous time correlated phase difference data set for eachfrequency in the “comb”. This simultaneous capture of phase data frommultiple frequencies may yield significant advantages for separating thedesired information about the patient's brain fluids from motionartifacts or other effects that would affect an individual scan of thefrequency where the phase data for each frequency is measured atdifferent times. Sampling each frequency at different times in this caseintroduces noise that may be difficult to detect or remove.

As the signal used to generate the magnetic field is typically periodic,it may not be necessary to use a sampling frequency that is many timesgreater than the frequency of that signal to capture the phaseinformation from a single cycle of the waveform, and instead anunder-sampling technique may be employed in some examples.Under-sampling is similar to heterodyning techniques used in modernradios where a large portion of amplifier gain and the audio or videosignal demodulation is performed in much lower intermediate frequencystages of the electronics (IF). Under-sampling, in effect, allows asystem to collect the same or a similar number of sample points over alonger period of time, while not disturbing the phase information of thesignal.

Using under-sampling may eliminate the need for high-speed A to Dconverters (which are expensive and may involve many different wiredconnections) that may otherwise be required to capture enough phasesamples from a single cycle of the waveform to accurately measure phaseangle. If a lower speed A to D converter may be used, it may becommercially and physically practicable to position the A to D converter122, 126 proximate the transmitter 120 and receiver 124 loops 250, 270,as described above.

Therefore, in some embodiments, one or both of the transmitted andreceived magnetic field signals may be under-sampled (e.g., with onesample or less for each cycle) and an average record of the waveform maythus be captured using samples taken over a much longer interval of timecompared to one cycle. In order to accomplish the under-sampling, boththe transmit signal and the sampling signal may be derived from a commonclock signal, with the sampling signal being accurately offset from thetransmit signal frequency (or a sub-harmonic frequency) by a smallamount. If the offset is, for example, 10 KHz from the first harmonicfrequency of the transmit signal, the result after a period of 100microseconds will be an effective picture of one cycle of the repetitivetransmit waveform with f/10000 individual samples. For a transmit signalfrequency of 100 MHz and sample frequency 100.010 MHz, the 10,000under-sampled individual samples of a single cycle of the transmitwaveform are spaced at a resolution of 360/10000 or 0.036 degrees. Asone alternative to under-sampling, frequency conversion using standardnon-linear mixing technology before an A to D converter 122, 126 mayalso be employed.

In other examples, the frequency of the magnetic field generator signaland the frequency of the sampling signal may be otherwise related, oneexample of which is described below when referring to frequency domainsignal processing techniques. In still other examples, the samplingfrequency may be relatively constant (e.g., 210 MHz, while thegenerating frequency may vary over a wide range).

Conversion of the Transmitted and Received Analog Signals to DigitalData

In some embodiments, electronic phase shift measurements between thetransmit and receive signals may be performed using analog signalprocessing techniques, whereas in other examples the phase shiftmeasurements may be performed after converting the analog data todigital data through one or more A to D converters 122, 126, asdescribed above. The digital waveforms may then be processed to obtainthe relevant phase shift information. Processing digital data ratherthan analog data may facilitate sampling and averaging many cycles ofthe waveforms in order to, for example, reduce the effects of randomnoise and, with proper techniques, even reduce non-random periodic noisesuch as AC line pickup at frequencies near 60 Hz. Also, after reducingthe noise in the waveform data there are many methods, such ascorrelation, that may be employed to obtain accurate phase measurementusing digital signal processing.

In some examples of the diagnostic system 100 described herein, the A toD conversion of both the transmitted and the received signals isperformed as close as feasible to the point of generation and/ordetection of the magnetic fields. For example, the A to D conversion mayperformed in the headpiece 106 by miniaturized monolithic single chip Ato D converters 122, 126 located integral to the printed circuits that,respectively, contain the transmitter 120 and receiver 124. The A to Dconverter 122 for the transmitter 120, for example, may differentiallysample the voltage across the balanced outputs of the transmitter 120 inone example. The A to D converter 126 for the receiver 124, for example,may be positioned at the output of a wide bandwidth signal amplifiercoupled to the receiver 124. By locating the A to D converters 122, 126on the headpiece 106 rather than in a remote processing unit 104 (whichmay, however, be done in other embodiments described herein) it may bepossible to reduce or eliminate the effects of phase shifts associatedwith motion, bending, or environmental changes on the cables carryingthe analog signals to the A to D converters 122, 126. Other sources oferror that may be reduced or eliminated include cable length relatedstanding-wave resonances due to small impedance mismatches at theterminations and cross-coupling between the transmit and receive signalson the interconnecting cables that generate phase errors due to waveformdistortion. To realize similar advantages in an embodiment where the Ato D converters 122, 126 are not located proximate the transmitter 120and receiver 124, a single cable may be used to bring the samplingsignal to the transmitter and receiver A to D converters 122, 126 in theprocessing unit 104, and/or a high quality semi-rigid cable may be usedbetween the two A to D converters 122, 126 in some embodiments.

Overall Operation and Pipelining

Referring again to FIG. 1, the waveform data (which may be under-sampledin some embodiments) may be captured for both the transmitted andreceived magnetic fields, and the captured waveforms may be at leastpartially processed in real-time (or substantially real-time). Asdescribed herein, one FPGA 112 may average the data for each of the twowaveforms over many cycles for noise reduction. Another FPGA 114 maythen use a correlation technique to perform a phase shift measurementusing the averaged waveform data. A pipelining technique may be used insome embodiments to speed up the data throughput for collection of phasedata over multiple frequency samples. The transmitter 120 may generate atime-varying magnetic field at a first desired frequency, and therequisite number of waveform averages may be performed by the waveformaverager FPGA 112 at this first frequency.

After the averager FPGA 112 collects and averages all of the sample datapoints from the transmitter 120 and receiver 124, it may transfer thesame to the phase shift measurement FPGA 114. In some embodiments, onlya single transmit frequency is used in diagnosing a fluid change in apatient, but in other embodiments, a plurality of different transmitfrequencies within a desired spectral range may be generated and thecorresponding data collected. In those embodiments with multipletransmit frequencies, phase determination for a first transmit frequencymay proceed in the phase shift measurement FPGA 114 (using the dataacquired during the first transmit frequency) while the frequencysynthesizer FPGA 110 causes the transmitter 120 to generate a magneticfield having a second desired frequency of the spectral scan and thewaveform data from the second transmit frequency is averaged by thewaveform averager FPGA 112 (hence the pipelining). In other embodiments,the waveform averaging for one transmit frequency may occursubstantially simultaneously with recording a plurality of samples for asecond frequency. In general, many different types of pipelining (e.g.,performing two or more parts of the signal generation, acquisition, anddata processing at substantially the same time) may be used. In otherembodiments, however, there may not be any pipelining, and thediagnostic system 100 may transmit, collect, average, and process all ofthe data relating to a single transmit frequency before moving to asecond transmit frequency.

Regardless of whether pipelining is used, the process of using differenttransmit frequencies may be repeated for any number of transmitfrequencies with a desired spectral frequency scan, and may also berepeated for one or more frequencies within the spectral scan. Thecalculated phase shifts for each frequency may be transferred to thelaptop 102 directly from the phase shift measurement FPGA 114 in someexamples.

Signal Processing—Averaging

Because of the relatively small size of the transmitter 120 and thereceiver 124, as well as the relatively low power of the transmittedmagnetic field (it is low power because of, among other things, the needto protect a patient from overexposure to RF radiation and the need tominimize electromagnetic field emissions from the system 100), themeasured magnetic field at the transmitter 120 and/or at the receiver124 may have relatively large amounts of noise compared to itsrelatively small amplitude. The noise may include input thermal noise ofan amplifier, background noise from EMI pickup, and so forth. In someembodiments, the noise may contribute a significant fraction to thephase shift measurements relative to the actual phase shift. Forexample, 1 ml of fluid change may correspond with a 0.3 degree phaseshift, and thus if the noise in the transmit and receive signals is asubstantial portion of, or even exceeds, the expected phase shift, thenoise may render the data unacceptable.

In order to reduce the noise, the diagnostic system 100 described hereinmay, in some embodiments, sample many cycles of the transmitted andreceived magnetic fields (e.g., many multiples of 10,000 samples, suchas 32,000 samples) and may average the individual samples in order tosubstantially reduce random noise. In some examples, the total samplingtime interval may be extended to be an approximate integer multiple ofone 60 Hz AC power period in order to reduce the effect of 60 Hz relatedelectromagnetic interference pickup. As explained below, these waveformsmay be averaged by any appropriate averaging technique, includingmultiplying them by one another in the time domain, as well as otherfrequency domain averaging techniques.

Referring now to FIG. 4, one embodiment 300 of a simplified logicdiagram of the waveform averager FPGA 112 is shown. Of course, in otherembodiments, custom circuitry may be employed to average data, whichcustom circuitry may be located in headpiece 106, in processing unit104, in laptop 102, or in another suitable location. FIG. 4, however,illustrates one example of logic that may be implemented in the waveformaverager FPGA 112 for averaging the transmitted waveform samples afterthey have been digitized by an A to D converter. Similar logic 300 maybe used to average the received waveform samples after they have beendigitized. The input to the waveform averager FPGA 112 may be a LowVoltage Differential Signaling (LVDS) type of format from the A to Dconverter, in order to reduce the wiring needed between an A to Dconverter and the waveform averager FPGA 112. In the LVDS format, eachword of digital data representing a single waveform data-point may firstbe converted from serial data to parallel data by the deserializationlogic described below.

The logic illustrated in FIG. 4 includes a synchronous serial-in,parallel-out shift register 301 that is clocked by the data transferclock from the A to D converter. The parallel data words are thentransferred into a memory buffer 302 with sufficient capacity to handlethe maximum number of individual waveform samples required to constructone complete cycle of the transmitted waveform. An adder 303 may be usedto accumulate the sum of all of the waveform samples in the memorybuffer 302 as the data words exit the register 301 or after the memorybuffer 302 is fully populated. Each waveform sum memory location mayhave a word size in bits that can accommodate the largest numberexpected for the sum without overflow. For example, a 12 bit resolutionA to D converter and 4096 waveform sum requires a 24-bit memory wordsize. After accumulating the sum of the intended number of waveforms inthe waveform memory for the transmitted signal samples (and, separately,the receiver signal samples are similarly summed in a waveformaverager), the memory contents for both waveforms are seriallytransferred to the phase shift measurement FPGA 114. It may not benecessary to divide by the number of waveforms being averaged in someexamples because, in the next step of the processing, only the relativemagnitudes of the data-points in the averaged waveforms may be relevant.Because of this, an appropriate number of least significant bits mayalso be deleted from each of the averaged waveform data points withoutsignificant impact to the accuracy of the overall phase shiftdetermination.

Signal Processing—Determining Phase Shift

Referring now to FIG. 5, the phase shift measurement FPGA 114 may alsocontain two revolving shift registers 401, 402, a multiplier 403, and anadder 404. It may also include logic configured to calculate the sum ofthe product of the individual transmit and receive averaged waveformdata points with an adjustable phase shift between the two waveforms.The FPGA may be used to find the phase shift where the sum of productsis closest to zero and the slope of the sum of products versus phaseshift is also negative.

Consider the following trigonometric identity for the product of twosine waves with frequency f and phase shift ϕ:

$\begin{matrix}{{{\sin \; u\; \sin \; v} = {1\text{/}{2\lbrack {{\cos ( {u - v} )} - {\cos ( {u + v} )}} \rbrack}}}\mspace{14mu} {where}\mspace{14mu} {u = {{{2\pi \; f\; t} + {\Phi \mspace{14mu} {and}\mspace{14mu} v}} = {2\pi \; f\; t}}}} & ( {{Eq}.\mspace{11mu} 1} ) \\{= {1\text{/}{2\lbrack {{\cos (\Phi)} - {\cos( {{2{\pi ( {2f} )}t} + (\Phi)} \rbrack}} }}} & ( {{Eq}.\; 2} )\end{matrix}$

The first term of the product is a DC term dependent only on the phaseshift. The second term is another sine wave at twice the frequency whichaverages to zero over one complete cycle of the original frequency. Notethat the first term (a cosine wave) is also zero when the phase angle(ϕ) is either +90° or −90°. Furthermore the slope of the product withrespect to phase angle change d(sin u sin v)/dϕ is negative for ϕ=+90°and positive at ϕ=−90°.

By iteration, the FPGA may determine the value of noffset where thetransmitted wave and received wave are closest to a +900 phase shift.For an offset of noffset samples, and nt samples for one complete 360°waveform, the phase shift is then calculated using the followingequation:

Phase shift=90°+(noffset/nt)*360°  (Eq. 3)

The resolution of the determination may be limited to the number ofsamples (resolution=360°/nt). If this resolution is insufficient for theneeded precision of the measurement, then interpolation may be used tofind the fractional value of noffset where the sum of product termsexactly passes through zero.

Frequency Domain Signal Processing Methods for Phase Shift Measurement

As explained above (see e.g., sections on averaging and multiplyingwaveforms together to obtain phase shift data), the signal processing ofthe measured and digitized magnetic field traces from both thetransmitter 120 and the receiver 124 may proceed in the time domain. Inother embodiments, however, the signals may be processed in thefrequency domain using, for example, fast Fourier transforms (FFTs)

In one embodiment of Fourier domain analysis, the signals from thetransmitter 120 and receiver 124 are digitized at, for example, about a200 MHz sampling rate with a relatively high resolution (e.g., 14 bits).The A to D converter and the data capture electronics may be included ina relatively small printed circuit assembly packaging. The captured datamay be transferred via a high-speed USB serial link to the laptopcomputer 102. Time domain processing can then be replaced byfrequency-domain processing on the laptop 102 to calculate the phaseshift between the waveforms.

Once the data is on the laptop 102, the FFT for each of the transmitterand receiver time domain waveforms can be calculated (in otherembodiments, however, the FFT may be calculated by an FPGA or otherprocessor proximate the A to D converters). The resulting real andimaginary solutions which represent the resistive and reactive frequencydomain data can then be converted from Cartesian to polar coordinates,thus yielding frequency domain plots of the magnitude and phase of thewaveforms. The phase of each waveform can be obtained from the frequencydomain plots of phase for the frequency of interest. If the fundamentalfrequency is off-scale, then a difference frequency between the samplingfrequency and the transmitted wavefield frequency can be used. Forexample, a sample frequency of 210 MHz yields an FFT with a frequencyrange of 0 to 105 MHz, and the fundamental frequency is used for phaseshift measurement when the transmitted wavefield frequency lies in thisrange. The difference frequency is used if the transmitted wavefieldfrequency is in the higher end of the range, for example, 105 MHz to 315MHz.

After the FFT for both of the transmitted and received wavefield signalsis calculated, the phase shift for a particular frequency of interestcan then be calculated from the difference of the phase values obtainedfrom the transformed transmitter and receiver waveforms. Note that somesign reversals for the phase information in various frequency regionsmay be needed when calculating the shift.

In order to allow FFTs to be computed for samples from the transmitter120 and the receiver 124, the frequencies used for the sampling and thetransmitted waveform may be determined so as to allow coherent samplingso that both the transmitted and received waveforms contain an integernumber of complete time periods of the repeated waveform, and the numberof samples collected for the waveforms is an even power of two. Onemethod for implementing coherent sampling is to choose transmitter andreceiver sampling frequencies such thatprime1/ftransmit=prime2/freceive. The prime numbers prime1 and prime2,as well as the number of samples, can be very large in some embodiments,thereby reducing the spacing between the allowable values for the signalfrequencies (e.g., the tuning resolution may be approximately 1 Hz).This may be accomplished by using digital frequency synthesistechniques, such as by combining a stable frequency source and theappropriate combinations of integer frequency multipliers, integerfrequency dividers, and phase lock loops.

With coherent sampling, the theoretical accuracy of the phasecalculation may only be limited by the number of samples of the timedomain waveform and the digital resolution of the A to D converter. DCnoise and low frequency noise sources such as 1/f noise may beinherently rejected by the frequency domain processing technique. Theuse of coherent sampling also reduces the probability that harmonic andintermodulation product frequency components will lie on top of thefrequencies of interest for calculating phase. Furthermore, using an FFTfrequency domain solution to determining phase may provide informationregarding the magnitude or amplitude of the measured transmitted andreceived magnetic fields. The ratio of the magnitude values can be usedto determine the attenuation of the transmitted magnetic field, whichmay be expressed in logarithmic dB power ratio units.

Alternative Signal Processing in the Time Domain

As one additional alternative signal processing technique in the timedomain, the phase shift measurement may be done via one or morerelatively low-cost analog phase detectors or by measuring time delaysbetween zero crossings of the transmitted and received wavefieldsignals. For example, an integrated phase detector circuit may includean amplifier that converts sine waves of transmitted and receivedwavefields to square waves by clipping the sine waves (e.g., with anextra high gain), and then compares the clipped/square wave from thetransmitter with that from the receiver using an analog exclusive OR(XOR) gate, with the pulse width provided by the XOR gate beingindicative of the phase shift between the transmitted and receivedmagnetic fields.

Reduction of Phase Measurement Errors due to Motion

Among all of the factors that contribute to phase measurement error,many are related to motion—motion of the patient, movement of thetransmitter 120, movement of the receiver 124, bending of the connectionor transmission cables, etc. For example, relative motion between thepatient and the transmitter 120/receiver 124 results in path length andlocation variations for the magnetic field lines as they pass throughthe patient's head. Conductive or magnetic objects moving near thetransmitter 120 and/or near the receiver 124 can also change the shapeof the magnetic field lines as they pass from the transmitter 120 to thereceiver 124.

In some embodiments, methods may be deployed to reduce artifactsattributable to patient movement. These algorithms may, for example,detect statistical variations in the differential phase shift dataacross the frequency spectrum of interest (e.g., from about 30 MHz to300 MHz or about 20 MHz to 200 MHz) that could not possibly be theresult of biological changes, as determined by their rates of change orother characteristics. This thresholding-type of method may thus be usedto eliminate data corrupted by means other than true biological changes.

As another example, the attenuation data that is obtained from themagnitude portion of the FFT processing can be utilized in algorithms byexamining the way it varies across the frequency spectrum to aid in thedetection and correction of motion artifacts in the phase shift data.

As still another example, electronic accelerometers can additionally oralternatively be used to detect motion of one or more of the transmitter120, the receiver 124, the patient, or the transmission cables. In someexamples, accelerometers may be coupled to the same printed circuitboard as the transmitter or receiver (e.g., using a MEMS typeaccelerometer).

In addition to detecting any motion above a threshold level, arelationship between the transmitter/receiver accelerometer data andpatient accelerometer data may be examined for relative differences. Forexample, small amplitude changes sensed in both the patient and thetransmitter/receiver may be of little consequence. Some patient motionis almost always present (because, e.g., even comatose patientsbreathe). Larger or non-correlated accelerometer readings, however, maybe used to trigger data rejection or correction. Because the separatemotion of totally independent objects near the patient can also presentmotion artifacts in the data then some types of motion detection andcorrection based on statistical analyses of the phase data may still berequired.

Medical Diagnostic Methods for Alerting Clinicians

The system 100 described herein may be used to, among other things,measure the change in phase shift induced by changes in fluid contentwithin, for example, a patient's head (“intracranial fluid”). Methodscan be employed to analyze the phase data and make a determination as towhether the fluid change represents a tissue change that is troubling tothe clinician user. For example, a baseline reading of the phase shiftbetween a magnetic field transmitted from a transmitter 120 positionedon one side of a patient's head and a magnetic field received at areceiver 124 positioned on the other side of the patient's head at oneor more frequencies may be recorded when the patient first arrives atthe hospital. Then, any significant changes in the measured phase shiftthat occurs during subsequent scans can be tracked and trended byclinicians to aid in understanding the patient's clinical condition, andcertain thresholds, patterns or trends may trigger an alarm. Manymethods may be employed and optimized to provide the clinicians with themost useful fluid change information. For example, if the phase shiftsby more than a certain number of degrees, the system may sound an alarmto alert the clinician that the patient may have clinically significantbleeding or edema. For some conditions, it may be useful to alert theclinician if the rate of change of the phase shift exceeds a threshold.

The phase shifts at different frequencies may vary with different fluidchanges, as described, for example, U.S. Pat. No. 7,638,341, which ishereby incorporated by reference in its entirety for all purposes.Certain patterns of phase shift may be correlated with certain clinicalconditions. For example, a condition such as bleeding or edema may beevidenced by an increase in phase angle at one frequency, with aconcurrent decrease at a different frequency. Using ratios of phaseshifts at different frequencies can provide additional information aboutthe types of fluids and how they are changing. For example, the ratio ofphase shift at a first frequency to the phase shift at a secondfrequency may be a good parameter to assess blood content or to separateedema from bleeding or other fluid change. For example, the phase shiftfrequency response of saline may be different from the phase shiftfrequency response of blood, thus allowing a clinician to separatelyidentify changes in blood and saline content in a patient's braincavity. Changes in amounts of water may have relatively little effect onphase shift in some instances, although the concentration ofelectrolytes in an ionic solution may have a more pronounced effect.

The phase shift patterns may also be time dependent. A hypotheticalclinical condition may be characterized by an increase in phase shiftfor some period of time, then stabilizing, and then returning tobaseline after some other time period. Noise factors such as patientactivities like getting up out of bed, eating, getting blood drawn orspeaking with visitors may cause changes to the phase shift readingsfrom baseline. Clinically meaningful fluid changes may be differentiatedfrom noise by examining the patterns associated with differentactivities.

Using combinations of phase shift data at various frequencies, ratios orother functions of those phase shifts, and/or time-based methods may allbe combined and optimized in various embodiments to provide a range ofuseful information about tissue and/or fluid changes to clinicians. Theclinicians can then respond to the tissue changes by using more specificdiagnostic techniques such as medical imaging to diagnose a clinicalproblem.

In some cases, therapies may be changed in response to fluid and/ortissue change information. For example, the diagnostic system describedherein may monitor fluid changes in a patient who is on blood thinnersto dissolve a clot in a cerebral artery. If the system detects anintracerebral bleed, the blood thinners may be reduced or stopped tohelp manage the bleeding, or other interventions such as vascularsurgery may be performed to stop the bleeding. As another example, apatient who begins to experience cerebral edema may undergo medicalinterventions to control or reduce the edema, or can undergo surgicalprocedures to drain fluid or even have a hemicraniectomy to reduceintracerebral pressure due to the edema.

Clinicians may, in some cases, use fluid change information to managemedication dosage by examining what is effectively feedback from thediagnostic system. For example, if mannitol is used to reduceintracerebral pressure by drawing water out of the brain, a treatingclinician may use the diagnostic system described herein in order toreceive feedback regarding how the patient's brain water is changing inresponse to the medication.

Similarly, drugs for blood pressure management, electrolyteconcentration and other parameters may be more effectively administeredwhen dosage amounts are controlled responsive to feedback from thediagnostic system described herein. For example, cerebral sodiumconcentrations may be controlled using intravenous hypertonic orhypotonic saline solutions. Changes to the ion concentrations can bedetected as a shift in phase angle or some function of shift in phaseangle at one or more frequencies. Such information can be used asfeedback to the physician to better manage the patient.

Although specific embodiments of the disclosure have been describedherein for purposes of illustration, various modifications may be madewithout deviating from the spirit and scope of the disclosure. Forexample, although the present application includes several examples ofmonitoring fluid changes in the human brain as one potential applicationfor the systems and methods described herein, the present disclosurefinds broad application in a host of other applications, includingmonitoring fluid changes in other areas of the human body (e.g., arms,legs, lungs, etc.), in monitoring fluid changes in other animals (e.g.,sheep, pigs, cows, etc.), and in other medical diagnostic settings.Fluid changes in an arm, for example, may be detected by having an armwrapped in a bandage that includes a transmitter and a receiver.

A few examples of the other medical diagnostic settings in which thesystems and methods described herein may be used include determining anabsolute proportion of a particular fluid, tissue (e.g., muscle, fat,parenchymal organs, etc.), or other solid matter (e.g., a tumor) in agiven area of a human body, determining relative permittivity and/orrelative permeability of an object, and so forth. Further clinicalapplications include a wide variety of monitoring and diagnostic uses,including internal bleeding detection, distinction between differenttypes of fluid (e.g. blood, extracellular fluid, intracellular fluid,etc.), assessing edema including cerebral edema as well as lymphedemaand lung fluid build-up resulting from such conditions as congestiveheart failure. All of these applications and many more may be addressedby various embodiments described herein. Accordingly, the scope of theclaims is not limited to the specific examples given herein.

What is claimed is:
 1. A diagnostic method for monitoring changes in afluid medium in a patient's head, the method comprising: positioning atransmitter at a first location on or near the patient's head, whereinthe transmitter is configured to generate and transmit a time-varyingmagnetic field into a fluid medium in the patient's head responsive to afirst signal; positioning a receiver at a second location on or near thepatient's head offset from the transmitter and configured to generate asecond signal responsive to a received magnetic field at the receiver;transmitting from the transmitter a time-varying magnetic field into thefluid medium in the patient's head in response to the first signal;receiving at the receiver the transmitted magnetic field; generatingwith the receiver the second signal responsive to the received magneticfield; and determining, using a processing unit coupled with at leastthe receiver, a phase shift between the transmitted magnetic field andthe received magnetic field for a plurality of frequencies of thetransmitted time-varying magnetic field; wherein at least one of thetransmitter or the receiver comprises a shielded transmission line, andwherein the shielded transmission line comprises a strip line on aprinted circuit board coupled between two grounded planes and has a loopshape.